1. Technical Field
This document relates to heart valve xenografts, and more particularly to heart valve xenografts from animals having a disruption in the endogenous α1-3 galactosyl transferase nucleic acid sequence.
2. Background Information
Prosthetic heart valves are used to replace damaged or diseased heart valves, including the aortic, mitral (bicuspid), tricuspid, and pulmonary heart valves. There are two basic types of prosthetic heart valves, mechanical and tissue valves. Mechanical heart valves use a pivoting mechanical closure to provide unidirectional blood flow. Mechanical valves do not wear out but they require life-long anticoagulation, with an increased incidence of thrombotic and hemorrhagic complications.
Tissue valves resemble native valves, and do not require life-long anticoagulation, but they wear out over time (in general after about 10 years). Much of the structure and many of the properties of original heart valves can be retained in transplants through use of heterograft (i.e., from the same species as the graft recipient) or xenograft (i.e., from a different species than the graft recipient) heart valve or heart tissue materials. Once implanted in an individual, a xenograft provokes hyperacute rejection (HAR), which occurs within minutes to hours of implantation. HAR can be overcome by a number of methodologies. If HAR is avoided, the organs can be rejected within a few days to weeks, even in the presence of a regimen of immunosuppressive agents that are effective at preventing allograft rejection. Xenografts can be chemically treated to reduce immunogenicity prior to implantation into a recipient or subjected to various physical treatments in preparation for implantation.
Heart valve xenografts typically are harvested from pig or cow heart tissues. Pig valves are often left intact and used as a direct replacement for the damaged valve of the recipient. Bovine heart valve xenografts are often made with bovine pericardium. Bovine heart valve xenografts are stronger than porcine xenografts but implant rejection is still a problem.